What is the mechanism of action of this treatment?

Common treatments for blood cancers, such as Donor Lymphocyte Infusion (DLI), work by enhancing the body's immune response to target and eliminate cancer cells. DLI involves infusing lymphocytes from a donor into the patient to boost the graft-versus-tumor effect, which helps in reducing the risk of relapse by attacking residual cancer cells. Other treatments, like CAR-T cell therapy, modify a patient's T cells to better recognize and destroy cancer cells. These therapies are crucial for blood cancer patients as they offer targeted approaches to eradicate cancer cells, potentially leading to longer remission periods and improved survival rates.

What side effects are associated with this type of intervention?

Common treatments for blood cancers, such as low-dose total body irradiation (LDTBI), allogeneic hematopoietic stem cell transplantation (HCT), and donor lymphocyte infusion (DLI), are associated with several side effects. LDTBI can cause asymptomatic thrombocytopenia, while allogeneic HCT often leads to graft-versus-host disease (GVHD), infections, and long-term complications like myelodysplastic syndrome and secondary malignancies. DLI, aimed at reducing relapse risk, can also exacerbate GVHD and increase the risk of infections. These treatments require careful monitoring and management of side effects to ensure patient safety and improve outcomes.

What prior FDA approvals exist?

FDA-approved treatments for blood cancers that enhance the immune response include Romiplostim, approved in 2021 for acute radiation syndrome, which is relevant for its role in hematopoietic recovery. Additionally, drugs like Rituximab, a monoclonal antibody used in various lymphomas, and Dasatinib, used in Philadelphia chromosome-positive acute lymphoblastic leukemia, have shown efficacy in enhancing immune responses. These treatments, while not identical to Donor Lymphocyte Infusion, share the goal of improving patient outcomes by modulating the immune system.

What other types of research exist?

Promising novel alternatives to Donor Lymphocyte Infusion for blood cancer patients include Chimeric Antigen Receptor (CAR) T-cell therapy, checkpoint inhibitors such as nivolumab and pembrolizumab, and bispecific T-cell engager antibodies like blinatumomab. These therapies have demonstrated efficacy in reducing relapse risk and improving outcomes in clinical trials.

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Alkylating agents

Donor Lymphocyte Infusion for Blood Cancers

Phase 1 & 2

Recruiting

Led By Christopher G Kanakry, M.D.

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Recipient must have at least one potentially suitable HLA-haploidentical or HLA-matched donor

Recipient must have a histologically or cytologically confirmed hematologic malignancy classified as high or very high disease risk

Must not have

Recipient must not have had prior myeloablative conditioning for autologous or allogeneic HCT

Recipient must not have active malignancy of non-hematopoietic type that is metastatic, relapsed/refractory, or locally advanced and not amenable to curative treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if giving white blood cells from a donor to patients with high-risk blood cancers can reduce the risk of the cancer coming back. The goal is to see if this approach helps fight off remaining cancer cells and prevents relapse.

Who is the study for?

Adults aged 18-65 with high-risk blood cancers like leukemia, lymphoma, myelodysplastic syndrome, or multiple myeloma that are hard to treat or likely to come back. They need a healthy relative who can donate bone marrow and white blood cells for the study.

What is being tested?

The trial is testing if giving patients donor lymphocytes (white blood cells) from their transplant donor soon after a bone marrow transplant can lower the chance of cancer coming back. It includes chemotherapy drugs and staying near NIH for monitoring.

What are the potential side effects?

Possible side effects include reactions to donor cells, increased risk of infections due to immune suppression from chemotherapy and other medications used in the process, as well as typical chemo-related issues like nausea, fatigue, hair loss.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have a donor who matches my HLA type.

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My blood cancer is confirmed to be at a high or very high risk.

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I can care for myself but may need occasional help.

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I am between 18 and 65 years old.

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My heart, lungs, kidneys, and liver are functioning well.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not undergone intense bone marrow preparation for stem cell transplant.

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I do not have an active, spreading, or untreatable cancer besides blood cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

determine the maximally tolerated dose of DLI that can be safely administered after HLA-matched-related HCT and after HLA-haploidentical HCT

Secondary study objectives

determine, at the maximally tolerated dose in the phase II portion of the study, the cumulative incidences of Grades II-IV and Grades III-IV aGVHD at days +100 and +200 for HLA-matched-related and HLA-haploidentical

determine, at the maximally tolerated dose in the phase II portion of the study, the cumulative incidences of Steroid-refractory Grades II-IV and Grades III-IV aGVHD at days +100 and +200 for HLA-matched-related and HLA-haploidentical

determine, at the maximally tolerated dose in the phase II portion of the study, the cumulative incidences of chronic GVHD at 1 year for HLA-matched-related and HLA-haploidentical

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Active Control

Group I: Phase II Efficacy, Cohort 2 (haploidentical)Experimental Treatment6 Interventions

DLI at maximally tolerated, safe dose (from Phase I) to assess secondary clinical outcomes at this dosing level (up to 14 additional evaluable patients in each cohort)

Group II: Phase II Efficacy, Cohort 1 (matched)Experimental Treatment6 Interventions

DLI at maximally tolerated, safe dose (from Phase I) to assess secondary clinical outcomes at this dosing level (up to 14 additional evaluable patients in each cohort)

Group III: Phase I Dose Escalation, Cohort 2 (haploidentical)Experimental Treatment6 Interventions

DLI at escalating doses (1 x 10\^5 CD3+ cells/kg, 3 x 10\^5 CD3+ cells/kg, and 1 x 10\^6 CD3+ cells/kg) on day +7 or +21 to assess for safety and determine Phase II dose (up to 18 evaluable patients)

Group IV: Phase I Dose Escalation, Cohort 1 (matched)Experimental Treatment6 Interventions

DLI at escalating doses (1 x 10\^6 CD3+ cells/kg, 3 x 10\^6 CD3+ cells/kg, and 1 x 10\^7 CD3+ cells/kg) on day +7 or +21 to assess for safety and determine Phase II dose (up to 18 evaluable patients)

Group V: Donor ArmActive Control1 Intervention

Donors for Recipients in Arms 1-4

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Sirolimus

2013

Completed Phase 4

~2750

Fludarabine

2012

Completed Phase 4

~1860

donor lymphocyte infusion

2016

Completed Phase 3

~260

Cyclophosphamide

2010

Completed Phase 4

~2310

Mycophenolate mofetil

2014

Completed Phase 4

~3060

Busulfan

2008

Completed Phase 4

~1710

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for blood cancers, such as Donor Lymphocyte Infusion (DLI), work by enhancing the body's immune response to target and eliminate cancer cells. DLI involves infusing lymphocytes from a donor into the patient to boost the graft-versus-tumor effect, which helps in reducing the risk of relapse by attacking residual cancer cells. Other treatments, like CAR-T cell therapy, modify a patient's T cells to better recognize and destroy cancer cells. These therapies are crucial for blood cancer patients as they offer targeted approaches to eradicate cancer cells, potentially leading to longer remission periods and improved survival rates.

Optimizing the Outcome of Anti-Myeloma Treatment with Daratumumab.Continuous Complete Remission in Two Patients with Acute Lymphoblastic Leukemia and Severe Fungal Infection Following Short-Term, Dose-Reduced Chemotherapy.